216 research outputs found
Fast Adaptation in Vestibular Hair Cells Requires Myosin-1c Activity
SummaryIn sensory hair cells of the inner ear, mechanical amplification of small stimuli requires fast adaptation, the rapid closing of mechanically activated transduction channels. In frog and mouse vestibular hair cells, we found that the rate of fast adaptation depends on both channel opening and stimulus size and that it is modeled well as a release of a mechanical element in series with the transduction apparatus. To determine whether myosin-1c molecules of the adaptation motor are responsible for the release, we introduced the Y61G mutation into the Myo1c locus and generated mice homozygous for this sensitized allele. Measuring transduction and adaptation in the presence of NMB-ADP, an allele-specific inhibitor, we found that the inhibitor not only blocked slow adaptation, as demonstrated previously in transgenic mice, but also inhibited fast adaptation. These results suggest that mechanical activity of myosin-1c is required for fast adaptation in vestibular hair cells
Energy Conversion via Metal Nanolayers
Current approaches for electric power generation from nanoscale conducting or semiconducting layers in contact with moving aqueous droplets are promising as they show efficiencies of around 30%, yet even the most successful ones pose challenges regarding fabrication and scaling. Here, we report stable, all-inorganic single-element structures synthesized in a single step that generate electrical current when alternating salinity gradients flow along its surface in a liquid flow cell. Nanolayers of iron, vanadium, or nickel, 10 to 30 nm thin, produce open-circuit potentials of several tens of millivolt and current densities of several microA cm^(−2) at aqueous flow velocities of just a few cm s^(−1). The principle of operation is strongly sensitive to charge-carrier motion in the thermal oxide nanooverlayer that forms spontaneously in air and then self-terminates. Indeed, experiments suggest a role for intraoxide electron transfer for Fe, V, and Ni nanolayers, as their thermal oxides contain several metal-oxidation states, whereas controls using Al or Cr nanolayers, which self-terminate with oxides that are redox inactive under the experimental conditions, exhibit dramatically diminished performance. The nanolayers are shown to generate electrical current in various modes of application with moving liquids, including sliding liquid droplets, salinity gradients in a flowing liquid, and in the oscillatory motion of a liquid without a salinity gradient
Energy Conversion via Metal Nanolayers
Current approaches for electric power generation from nanoscale conducting or
semi-conducting layers in contact with moving aqueous droplets are promising as
they show efficiencies of around 30 percent, yet, even the most successful ones
pose challenges regarding fabrication and scaling. Here, we report stable,
all-inorganic single-element structures synthesized in a single step that
generate electrical current when alternating salinity gradients flow along its
surface in a liquid flow cell. 10 nm to 30 nm thin nanolayers of iron,
vanadium, or nickel produce several tens of mV and several microA cm^-2 at
aqueous flow velocities of just a few cm s^-1. The principle of operation is
strongly sensitive to charge-carrier motion in the thermal oxide nano-overlayer
that forms spontaneously in air and then self terminates. Indeed, experiments
suggest a role for intra-oxide electron transfer for Fe, V, and Ni nanolayers,
as their thermal oxides contain several metal oxidation states, whereas
controls using Al or Cr nanolayers, which self-terminate with oxides that are
redox inactive under the experimental conditions, exhibit dramatically
diminished performance. The nanolayers are shown to generate electrical current
in various modes of application with moving liquids, including sliding liquid
droplets, salinity gradients in a flowing liquid, and in the oscillatory motion
of a liquid without a salinity gradient.Comment: Pre-edited final version, 16 pages main text, 5 figure
Energy Conversion via Metal Nanolayers
Current approaches for electric power generation from nanoscale conducting or semiconducting layers in contact with moving aqueous droplets are promising as they show efficiencies of around 30%, yet even the most successful ones pose challenges regarding fabrication and scaling. Here, we report stable, all-inorganic single-element structures synthesized in a single step that generate electrical current when alternating salinity gradients flow along its surface in a liquid flow cell. Nanolayers of iron, vanadium, or nickel, 10 to 30 nm thin, produce open-circuit potentials of several tens of millivolt and current densities of several microA cm^(−2) at aqueous flow velocities of just a few cm s^(−1). The principle of operation is strongly sensitive to charge-carrier motion in the thermal oxide nanooverlayer that forms spontaneously in air and then self-terminates. Indeed, experiments suggest a role for intraoxide electron transfer for Fe, V, and Ni nanolayers, as their thermal oxides contain several metal-oxidation states, whereas controls using Al or Cr nanolayers, which self-terminate with oxides that are redox inactive under the experimental conditions, exhibit dramatically diminished performance. The nanolayers are shown to generate electrical current in various modes of application with moving liquids, including sliding liquid droplets, salinity gradients in a flowing liquid, and in the oscillatory motion of a liquid without a salinity gradient
Motor Fatigue Measurement by Distance-Induced Slow Down of Walking Speed in Multiple Sclerosis
Background: Motor fatigue and ambulation impairment are prominent clinical features of
people with multiple sclerosis (pMS). We hypothesized that a multimodal and comparative
assessment of walking speed on short and long distance would allow a better delineation and
quantification of gait fatigability in pMS.
Objectives: To compare 4 walking paradigms: the timed 25-foot walk (T25FW), a corrected
version of the T25FW with dynamic start (T25FW+), the timed 100-meter walk (T100MW)
and the timed 500-meter walk (T500MW).
Methods: Thirty controls and 81 pMS performed the 4 walking tests in a single study visit.
Results: The 4 walking tests were performed with a slower WS in pMS compared to controls
even in subgroups with minimal disability. The finishing speed of the last 100-meter of the
T500MW was the slowest measurable WS whereas the T25FW+ provided the fastest
measurable WS. The ratio between such slowest and fastest WS (Deceleration Index, DI) was
significantly lower only in pMS with EDSS 4.0-6.0, a pyramidal or cerebellar functional
system score reaching 3 or a maximum reported walking distance !4000m.
Conclusion: The motor fatigue which triggers gait deceleration over a sustained effort in pMS
can be measured by the WS ratio between performances on a very short distance and the
finishing pace on a longer more demanding task. The absolute walking speed is abnormal
early in MS whatever the distance of effort when patients are unaware of ambulation
impairment. In contrast, the DI-measured ambulation fatigability appears to take place later in the disease course
Spatial and temporal control of Archean tectonomagmatic regimes
Secular trends in plutonic whole-rock geochemistry pose critical, although non-unique, constraints to early Earth tectonics. Here, we present a large whole-rock geochemical (879 collated samples) dataset for granitoids from the Pilbara Craton, Western Australia, applying it to test the link between secular trends and proposed tectonic mechanisms. We show that the spatio-temporal distribution of granitoid trace element geochemistry is constrained within discrete lithotectonic blocks supporting the reconstruction of its tectonomagmatic evolution. Time-sliced geochemical contour mapping of key petrogenetic ratios indicates the craton underwent rifting ∼3.2 Ga (billion years ago), marking a transition from predominantly sodic magmatism to a broader magmatic compositional spectrum. Our results demonstrate that rift-assisted breakup of proto-cratons is a viable craton growth mechanism. We identify a possible evolutionary sequence beginning with drips and upwellings below a Paleoarchean mafic plateau, which is subsequently dismembered by rifting. These plateau fragments form rigid blocks in the Mesoarchean, between which weaker, thinner crust accommodates minor convergence and divergence manifested as short-lived mobile lid-like features before stabilization. We conclude that these features do not require an active lid, plate tectonic regime
The stability of cratons is controlled by lithospheric thickness, as evidenced by Rb-Sr overprint ages in granitoids
The ancient cores of modern continents, cratons, are the oldest blocks of “stable” lithosphere on Earth. Their long-term survival relies on the resistance of their underlying thick, strong, and buoyant mantle keels to subsequent recycling. However, the effect of substantial geographical variations in keel thickness on the post-assembly behaviour and mass movement within these continental cores remains unknown. Here, we demonstrate that the spatial distribution of fluid-reset in-situ Rb-Sr ages for Paleo-Mesoarchean (3.6–2.8 billion years ago; Ga) granitoids of the Pilbara Craton, Australia shows remarkable correlation with independently-constrained lithospheric thickness models. Without craton-wide heating/magmatic events, these anomalously young Rb-Sr ages document episodes of fluid infiltration into granitoid complexes as a response to lithospheric reactivation by far-field stresses. This correlation implies that craton-wide fluid mobilization triggered by extra-cratonic Neoarchean to Mesoproterozoic (2.8–1.0 Ga) tectonic events is facilitated by variations in lithospheric strength and thickness. Compared to areas of older overprints, the two-thirds of the craton comprised of younger reset ages is underlain by comparatively thin lithosphere with higher susceptibility to reactivation-assisted fluid flow. We propose that even the strongest, most pristine cratons are less stable and impermeable than previously thought, as demonstrated by the role of granitoid complexes and cratons as selective lithospheric “sponges” in response to minor tectonic forces. Therefore, variations in lithospheric thickness, likely attained before cratonization, exert a crucial control on billions of years of fluid movement, elemental redistribution and mineralization within ancient continental nuclei
The effect of krill oil supplementation on skeletal muscle function and size in older adults: A randomised controlled trial
Background & aims The aim of this study was to determine the effect of krill oil supplementation, on muscle function and size in healthy older adults. Methods Men and women, aged above 65 years, with a BMI less than 35kg/m2, who participated in less than 1h per week of structured self-reported exercise, were enrolled in the study (NCT04048096) between March 2018 and March 2020. Participants were randomised to either control or krill oil supplements (4g/day) for 6 months in this double blind randomised controlled trial. At baseline, 6 weeks and 6 months, knee extensor maximal torque was measured as the primary outcome of the study. Secondary outcomes measured were grip strength, vastus lateralis muscle thickness, short performance physical battery test, body fat, muscle mass, blood lipids, glucose, insulin, and C-Reactive Protein, neuromuscular (M-Wave, RMS and voluntary activation), and erythrocyte fatty acid composition. Results A total of 102 men and women were enrolled in the study. Ninety-four participants (krill group (26 women and 23 men) and placebo group (27 women and 18 men)) completed the study (mean (SD): age 71.2 (5.1) years and weight 71.8 (12.3) kg). Six months supplementation with krill oil resulted in, an increase in knee extensor maximal torque, grip strength and vastus lateralis muscle thickness, relative to control (
Recommendations and guidelines from the ISMRM Diffusion Study Group for preclinical diffusion MRI: Part 1 -- In vivo small-animal imaging
The value of in vivo preclinical diffusion MRI (dMRI) is substantial.
Small-animal dMRI has been used for methodological development and validation,
characterizing the biological basis of diffusion phenomena, and comparative
anatomy. Many of the influential works in this field were first performed in
small animals or ex vivo samples. The steps from animal setup and monitoring,
to acquisition, analysis, and interpretation are complex, with many decisions
that may ultimately affect what questions can be answered using the data. This
work aims to serve as a reference, presenting selected recommendations and
guidelines from the diffusion community, on best practices for preclinical dMRI
of in vivo animals. In each section, we also highlight areas for which no
guidelines exist (and why), and where future work should focus. We first
describe the value that small animal imaging adds to the field of dMRI,
followed by general considerations and foundational knowledge that must be
considered when designing experiments. We briefly describe differences in
animal species and disease models and discuss how they are appropriate for
different studies. We then give guidelines for in vivo acquisition protocols,
including decisions on hardware, animal preparation, imaging sequences and data
processing, including pre-processing, model-fitting, and tractography. Finally,
we provide an online resource which lists publicly available preclinical dMRI
datasets and software packages, to promote responsible and reproducible
research. An overarching goal herein is to enhance the rigor and
reproducibility of small animal dMRI acquisitions and analyses, and thereby
advance biomedical knowledge.Comment: 69 pages, 6 figures, 1 tabl
Chemotherapy-resistant osteosarcoma is highly susceptible to IL-15-activated allogeneic and autologous NK cells
High-grade osteosarcoma occurs predominantly in adolescents and young adults and has an overall survival rate of about 60%, despite chemotherapy and surgery. Therefore, novel treatment modalities are needed to prevent or treat recurrent disease. Natural killer (NK) cells are lymphocytes with cytotoxic activity toward virus-infected or malignant cells. We explored the feasibility of autologous and allogeneic NK cell–mediated therapies for chemotherapy-resistant and chemotherapy-sensitive high-grade osteosarcoma. The expression by osteosarcoma cells of ligands for activating NK cell receptors was studied in vitro and in vivo, and their contribution to NK cell–mediated cytolysis was studied by specific antibody blockade. Chromium release cytotoxicity assays revealed chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cell lines and osteosarcoma primary cultures to be sensitive to NK cell–mediated cytolysis. Cytolytic activity was strongly enhanced by IL-15 activation and was dependent on DNAM-1 and NKG2D pathways. Autologous and allogeneic activated NK cells lysed osteosarcoma primary cultures equally well. Osteosarcoma patient–derived NK cells were functionally and phenotypically unimpaired. In conclusion, osteosarcoma cells, including chemoresistant variants, are highly susceptible to lysis by IL-15-induced NK cells from both allogeneic and autologous origin. Our data support the exploitation of NK cells or NK cell–activating agents in patients with high-grade osteosarcoma
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